Novel Protective Role of Myeloid Differentiation 1 in Pathological Cardiac Remodelling

被引:25
作者
Xiong, Xiaojv [1 ,2 ,3 ]
Liu, Yu [1 ,2 ,3 ]
Mei, Yang [1 ,2 ,3 ]
Peng, Jianye [1 ,2 ,3 ]
Wang, Zhiqiang [1 ,2 ,3 ]
Kong, Bin [1 ,2 ,3 ]
Zhong, Peng [1 ,2 ,3 ]
Xiong, Liang [1 ,2 ,3 ]
Quan, Dajun [1 ,2 ,3 ]
Li, Qi [1 ,2 ,3 ]
Wang, Guangji [1 ,2 ,3 ]
Huang, He [1 ,2 ,3 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan, Hubei Province, Peoples R China
[2] Wuhan Univ, Cardiovasc Res Inst, Wuhan, Hubei Province, Peoples R China
[3] Hubei Key Lab Cardiol, Wuhan 430060, Hubei Province, Peoples R China
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
基金
中国国家自然科学基金;
关键词
NF-KAPPA-B; ISCHEMIA-REPERFUSION INJURY; HYPERTROPHIC RESPONSE; SIGNALING PATHWAYS; ACTIVATION; EXPRESSION; MD-1; HEART; RP105; TOLL-LIKE-RECEPTOR-4;
D O I
10.1038/srep41857
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Myeloid differentiation 1 (MD-1), a secreted protein interacting with radioprotective 105 (RP105), plays an important role in Toll-like receptor 4 (TLR4) signalling pathway. Previous studies showed that MD-1 may be restricted in the immune system. In this study, we demonstrated for the first time that MD-1 was highly expressed in both human and animal hearts. We also discovered that cardiac-specific overexpression of MD-1 significantly attenuated pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of MD-1 had the opposite effects. Similar results were observed for in vitro angiotensin II-induced neonatal rat cardiomyocyte hypertrophy. The antihypertrophic effects of MD-1 under hypertrophic stimuli were associated with the blockage of MEK-ERK 1/2 and NF-kappa B signalling. Blocking MEK-ERK 1/2 signalling with a pharmacological inhibitor (U0126) greatly attenuated the detrimental effects observed in MD-1 knockout cardiomyocytes exposed to angiotensin II stimuli. Similar results were observed by blocking NF-kappa B signalling with a pharmacological inhibitor (BAY11-7082). Our data indicate that MD-1 inhibits cardiac hypertrophy and suppresses cardiac dysfunction during the remodelling process, which is dependent on its modulation of the MEK-ERK 1/2 and NF-kappa B signalling pathways. Thus, MD-1 might be a novel target for the treatment of pathological cardiac hypertrophy.
引用
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页数:13
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